基于網絡藥理學研究紅花抗心肌缺血的作用機制

李文靜 王艷萍 洪博

摘要 目的：構建紅花藥材-成分-靶點-通路網絡，探討紅花治療心肌缺血的作用機制。方法：以紅花中符合口服生物利用度（OB）≥30%、類藥性（DL）≥0.18的化合物作為研究對象，通過中藥系統藥理學數據庫與分析平臺（TCMSP）對進行檢索并得到靶點，并在UniProt數據庫靶點檢索基因名，通過GeneCards數據庫對心肌缺血進行檢索，得到心肌缺血靶點。將心肌缺血與紅花靶點取交集。將所得到交集靶點進行蛋白質-蛋白質相互作用（PPI）分析、基因本體（GO）富集分析和京都基因和基因組百科全書（KEGG）富集分析。利用Cytoscape 3.8.0軟件繪制藥材-化合物-靶點-通路網絡圖。結果：得到紅花16個活性成分，192個靶點，在GeneCards數據庫搜索并篩選得到335個心肌缺血靶點。得到紅花靶點與心肌缺血交集靶點58個。交集靶點PPI度值排名前3位為IL6、TNF、VEGFA。GO與KEGG通路富集分析分別選取前5個條目繪制氣泡圖。藥材-化合物-靶點-通路網絡中有89個節點，338條邊。節點前三的化合物為：槲皮素、山柰酚與木犀草素。結論：紅花可能通過多種化學成分、多靶點與多途徑起到治療心肌缺血的作用，為其在臨床使用提供理論依據。

關鍵詞 紅花;心肌缺血;冠狀動脈粥樣硬化心臟病;網絡藥理學;流體剪應力;槲皮素;通路網絡;作用機制

Study on the Mechanism of Carthamus tinctorius in Treatment of Myocardial Ischemia Based on Network Pharmacology

LI Wenjing，WANG Yanping，HONG Bo

（Department of Pharmacy，Qiqihar Medical University，Qiqihar 161006，China）

Abstract Objective：To construct Carthamus tinctorius medicinal material composition-target-pathway network and to explore the mechanism of Carthamus tinctorius in the treatment of myocardial ischemia.Methods：The compounds in Carthamus tinctorius which met OB≥30%，DL≥0.18 were taken as the research objects.The components and targets which met the requirements were searched by TCMSP Database，and the gene names of the targets were searched in UniProt Database.The myocardial ischemia targets were obtained by searching for myocardial ischemia in GeneCards Database.The intersection of myocardial ischemia target and Carthamus tinctorius target was obtained.The intersection targets were analyzed by PPI and GO and KEGG pathways.Cytoscape 3.8.0 software was used to draw the network diagram of medicinal drug-compound-target-pathway.Results：There were 16 active compounds and 192 targets in Carthamus tinctorius，and 335 targets of myocardial ischemia were obtained by searching for myocardial ischemia in GeneCards.Taking Carthamus tinctorius target and myocardial ischemia target as intersection，58 intersection targets were obtained.PPI analysis was performed on the intersection targets，and the top 3 targets with PPI score were：IL6，TNF，and VEGFA.The enrichment analysis of GO and KEGG pathways selected the first 5 entries to draw bubble charts.There were 89 nodes and 338 edges in the medicinal material-compound-target-pathway network.The top 3 compounds at the node were：quercetin，kaempferol and luteolin.Conclusion：Carthamus tinctorius may play a role in the treatment of myocardial ischemia through various chemical components，multiple targets and multiple ways，which provides theoretical basis for its clinical use.

Keywords Carthamus tinctorius; Myocardial ischemia; Coronary atherosclerotic heart disease; Network pharmacology; Fluid shear stress; Quercetin; Pathway network; Mechanism

中圖分類號：R256.22;R285文獻標識碼：Adoi：10.3969/j.issn.1673-7202.2022.10.005

心肌缺血（Myocardial Ischemia），是指心肌供血不足，隨之導致嚴重的并發癥且危及生命的疾病[1]。引起心肌缺血的原因主要有：主動脈供血減少、血黏度的變化、炎癥、冠脈阻塞以及心肌本身的病變等[2]。這些原因會導致心臟遭受急性缺血再灌注損傷，最終導致心律失常、心力衰竭和死亡[3]。……